Bone Marrow Transplantation最新文献

Immunological reconstitution after allogeneic hematopoietic cell transplantation (alloHCT) is critical for patient survival. We compared short- and long-term immune reconstitution and clinical endpoints in adult recipients of haploidentical or mismatched T cell replete peripheral blood stem cell transplants (PBSCT) with post-transplant cyclophosphamide as GvHD prophylaxis (PTCY, n = 68) to: (a) patients receiving matched unrelated grafts and anti-T lymphocyte globulin (ATLG) (MUD/ATLG, n = 280); (b) patients with a mismatched donor and ATLG (MM/ATLG, n = 54); and (c) recipients of matched related grafts without ATLG (MRD/NoATLG, n = 97). PTCY was associated with delayed neutrophil engraftment, low NK-cell counts on day 30 and reduced CD8+ cells on days 60-80. In terms of long-term reconstitution, PTCY recipients demonstrated significantly higher CD4+ counts from day 100-365, primarily derived from naïve T cells. Additionally, B-lymphocyte counts at one year were highest in the PTCY group. Early morbidity and mortality due to infectious complications (viral reactivation, (blood stream) infections) were most frequent in PTCY patients during the first three months. However, beyond three months, no PTCY patient suffered a fatal infection. Our study highlights the pattern of early immunodeficiency followed by robust long-term immune reconstitution in PTCY recipients, identifying critical time periods of risk that could be targeted to optimise patient survival and reduce infectious complications.

We aimed to prospectively explore the risk factors for measurable residual disease (MRD) positivity after allogeneic stem cell transplantation (allo-SCT) in AML patients (n = 478). The cumulative incidences (CIs) of post-SCT MRD positivity at 100 days, 360 days and 3 years were 4.6%, 12.1% and 18.3%, respectively. Positive pre-SCT MRD and pre-SCT active disease were risk factors for post-SCT MRD positivity at both 360 days and 3 years (P < 0.001). European LeukemiaNet (ELN) 2017 risk stratification was a risk factor for positive post-SCT MRD at 360 days (P = 0.044). A scoring system for predicting post-SCT MRD positivity at 360 days was established by using pre-SCT MRD, pre-SCT active disease and ELN 2017 risk stratification. The CI of positive post-SCT MRD at 3 years was 13.2%, 23.7%, and 43.9% for patients with scores of 0, 1, and 2, respectively (P < 0.001). Multivariate analysis demonstrated that the scoring system was associated with a higher CI of post-SCT MRD positivity, leukemia relapse and inferior survival. Our data indicate that positive pre-SCT MRD status, pre-SCT active disease, and ELN 2017 risk stratification are risk factors for positive post-SCT MRD status in AML patients.

In fit patients with newly diagnosed myeloma, high-dose chemotherapy (HDCT) followed by autologous stem cell transplantation (ASCT) is considered standard of care. For mobilization of CD34+ cells for ASCT, combined cytotoxic chemotherapy and G-CSF is commonly used. However, the importance of cytostatic chemotherapy for reliable mobilization remains unclear. This prospective randomized phase II non-inferiority trial compared G-GSF only (G) compared to standard chemotherapy/G-CSF (CG) for CD34+ mobilization. The primary endpoint was a less than 15% difference in successful stem cell collection ( ≥ 5.0 × 10⁶ CD34+ cells/kg b.w. in a single day collection procedure without additional stimulation with plerixafor) with the G regimen. 136 patients were 1:1 randomized. With an 18% difference in favor of the CG therapy, the non-inferiority margin was not maintained (95% CI 1%, 34%, p = 0.04). The median total CD34+ yield was 9.99 × 10⁶/kg b.w. in CG patients and 7.42 × 10⁶/kg b.w. in patients with G-CSF alone (p < 0.001). Ultimately, 130 (96%) patients proceeded to HDCT with ASCT. There were no differences in adverse events, hematologic engraftment, quality of life, or pain perception between the groups. Our data indicate that G-CSF only is inferior to chemotherapy with G-CSF for peripheral CD34+ stem cell mobilization. Trial registration SNCTP #: SNCTP000002952; Trials.gov #: NCT03442673.